Lectin-Modified Magnetic Nano-PLGA for Photodynamic Therapy In Vivo

Abstract

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.

Internalization of transferrin-tagged Myxococcus xanthus encapsulins into mesenchymal stem cells

“…Over the past decades, many different nanocarrier delivery systems were developed, e.g., gold [ 16 , 36 ] and iron oxide [ 37 , 38 ] nanoparticles, including those with metal-organic framework storages for drug and in vivo gene delivery [ 39 , 40 ]; micelles [ 41 ]; hybrid liposome-, polymer- [ 42 ], and protein-based nanoparticles [ 43 , 44 ]. The shells of such carriers can be modified by adding to their surface various receptor molecules to provide fast binding kinetics to the related ligand [ 45 ] and achieve specific targeting [ 46 ].…”

Internalization-Responsive Poly(lactic-co-glycolic acid) Nanoparticles for Image-Guided Photodynamic Therapy against HER2-Positive Breast Cancer

“…The “water–oil–water” double microemulsion synthesis method of PLGA nanoparticles proved its versatility for loading different substances – both hydrophobic and hydrophilic. ,,, To incorporate diagnostic modality into nanoparticles, we used the hydrophobic dye Nile Blue, a representative of the benzophenoxazine family, with microenvironment-sensitive fluorescence and high photostability . The HER2-positive imaging process was guided using the fluorescence properties of NB under excitation with infrared light.…”

Internalization-Responsive Nano-PLGA For Image-Guided Photodynamic Therapy Against HER2-Positive Breast Cancer

“…The “water-oil-water” double microemulsion synthesis method of PLGA nanoparticles proved its versatility for loading different substances – both hydrophobic and hydrophilic 19,26,50,51 . To incorporate diagnostic modality into nanoparticles, we used the hydrophobic dye Nile Blue, a representative of the benzophenoxazine family, with microenvironment-sensitive fluorescence and high photostability 52 .…”